Sitosterolemia is a genetic lipid storage disorder characterized by increased levels of sitosterol and other plant sterols in the plasma and other tissues due to increased non-selective intestinal absorption of sterols and decreased hepatic removal. Individuals having sitosterolemia can exhibit one or more of the following conditions: tendon and tuberous xanthomas, arthritis, hemolytic episodes, accelerated atherosclerosis and myocardial infarctions, and can die at an early age due to extensive coronary atherosclerosis. See Nguyen et al., “Regulation of cholesterol biosynthesis in sitosterolemia: effects of lovastatin, cholestyramine, and dietary sterol restriction”, Vol 32, Journal of Lipid Research, pp. 1941-1948, (1991), incorporated by reference herein.
Sitosterolemia can be treated with bile acid sequestrants (such as cholestyramine, colesevelam hydrochloride and colestipol), however, these compounds have a tendency to cause constipation in patients and therefore compliance with this treatment is difficult. Bile acid sequestrants (insoluble anion exchange resins) bind bile acids in the intestine, interrupting the enterohepatic circulation of bile acids and causing an increase in the fecal excretion of steroids. Use of bile acid sequestrants is desirable because of their non-systemic mode of action. Bile acid sequestrants can lower intrahepatic cholesterol and promote the synthesis of apo B/E (LDL) receptors which bind LDL from plasma to further reduce cholesterol levels in the blood.
Alternative treatments include ileal bypass surgery and selective low density lipoprotein plasmapheresis, which are physically undesirable for the patient.
An improved treatment for sitosterolemia is needed which can reduce the concentration of sterols in plasma and tissues and inhibit associated debilitating physical effects. Also, treatments which reduce the plasma or tissue concentration of non-cholesterol sterols such as phytosterols and 5α-stanols are needed.